Apparatus, method, and system for selectively effecting and/or killing bacteria

ABSTRACT

Certain exemplary embodiments of the present disclosure can provide an apparatus and method for generating at least one radiation can be provided. The exemplary apparatus and/or method can selectively kill and/or affect at least one bacteria. For example, a radiation source first arrangement can be provided which is configured to generate at least one radiation having one or more wavelengths provided in a range of about 190 nanometers (nm) to about 230 nm, and at least one second arrangement can be provided which is configured to prevent the at least one radiation from having any wavelength that is outside of the range can be provided.

CROSS-REFERENCE TO PRIOR APPLICATION(S)

This present application is a divisional application and claims priorityto U.S. patent application Ser. No. 14/021,631, filed on Sep. 9, 2013,which was issued as U.S. Pat. No. 10,071,262 on Sep. 11, 2018, whichclaims the benefit and priority from U.S. Provisional Application Ser.No. 61/450,038, filed on Mar. 7, 2011, and International Application No.PCT/US2012/027963, filed on Mar. 7, 2012, the disclosures of which areincorporated by reference herein in their entireties.

FIELD OF THE DISCLOSURE

Exemplary embodiments of the present disclosure relate to selectivelyaffecting and/or killing bacteria, and more specifically to exemplaryapparatus, methods and systems which can use an ultraviolet radiation toselectively affecting and/or killing bacteria while not harming humancells.

BACKGROUND INFORMATION

It has been estimated that between 2% and 5% of clean surgeries resultin surgical site infections (SSI). Patients who develop SSI can be 60%more likely to spend time in an ICU, can be 5 times as likely to bereadmitted, can have a mortality rate twice that of noninfectedpatients, can have an average of 7 days additional length of hospitalstay, and can have an average of about $3,000 additional costs. It hasbeen estimated that about 40-60% of SSIs can be preventable (see, e.g.,Barie P S, Eachempati S R. Surgical site infections. Surg Clin North Am2005; 85(6):1115-35, viii-ix).

It has been approximately 50 years since Deryl Hart and colleagues atDuke University showed that ultraviolet (UV) irradiation of surgicalwounds can be a highly effective methodology for reducing surgical woundinfection rates (see, e.g., Hart D. Bactericidal ultraviolet radiationin the operating room. Twenty-nine-year study for control of infections.J Am Med Assoc 1960; 172:1019-28). However, UV radiation can be a hazardboth to the patient and to the operating team, and the use of additionalclothing, hoods, and eye shields for protection can be both cumbersomeand costly, preventing widespread use of the technique.

UV radiation can be a very efficient bactericidal agent, and themechanisms by which it mutates and kills bacteria, as well as humancells, are well established (see, e.g., Mitchell D L, Nairn R S. Thebiology of the (6-4) photoproduct. Photochem Photobiol 1989;49(6):805-19; Witkin E M. Ultraviolet mutagenesis and inducible DNArepair in Escherichia coli. Bacteriol Rev 1976; 40(4):869-907; Koch-PaizC A, Amundson S A, Bittner M L, Meltzer P S, Fornace A J, Jr. Functionalgenomics of UV radiation responses in human cells. Mutat. Res. 2004;549(1-2):65-78; and Harm W. Biological effects of ultraviolet radiation.Cambridge, UK: Cambridge University Press, 1980). Ultraviolet germicidalirradiation (UVGI) has been used to break down microorganisms in food,air, and water purification. UVGI typically uses a short wavelength ofUV, typically in the UVB or UVC range, to destroy nucleic acids in smallorganisms, removing their reproductive capabilities. UV irradiation(including UVGI) is typically produced with low-pressure mercury lamps,which can produce a range of UV wavelengths, ranging from UVA(wavelengths 400 to 320 nm) to UVB (wavelengths 320 to 290 nm) to UVC(wavelengths 290 to 100 nm). FIG. 1 shows the spectrum of UV wavelengthsemitted from a typical mercury UV lamp. UVGI is typically produced bymercury-vapor lamps that emit at around 254 nm. However, UVGI lamps maybe harmful to humans and other life forms, and are typically shielded orin environments where exposure is limited.

UV lamps can also facilitate a UV emission from an excited moleculecomplex (e.g., an exciplex, such as either krypton-bromine orkrypton-chlorine), using arrangements called excilamps. The basic theorybehind exciplex UV emission was developed in the 1970s (see, e.g.,Lorents D C. A model of rare-gas excimer formation and decay and itsapplication to vuv lasers. Radiat. Res. 1974; 59(2):438-40; and MeasuresR M. Prospects for developing a laser based on electrochemiluminescence.Appl Opt 1974; 13(5):1121-33). The first excimer lasers were made in the1980s and they are now in common use, for example, e.g., in LASIKopthalmic surgery (see, e.g., Pallikaris I G, Papatzanaki M E, Stathi EZ, Frenschock O, Georgiadis A. Laser in situ keratomileusis. Lasers SurgMed 1990; 10(5):463-8). Current excimer lasers, however, are typicallynot feasible for wound sterilization both in terms of beam size (e.g.,excimer laser beams are very narrow) and their high cost. In the past,an excimer lamp (excilamp) has been developed in Russia (see, e.g.,Sosnin E A, Oppenlander T, Tarasenko V F. Applications of capacitive andbarrier discharge excilamps in photoscience. J. Photochem. Photobiol C:Photochem. Rev. 2006; 7:145-63), which can produce a wide high-intensitybeam of single-wavelength UV radiation. These lamps can be small,inexpensive (e.g., ˜$1,000), high powered (e.g., wound irradiation timecan be a few seconds), and long-lived (e.g., 1,000 to 10,000 hours).Certain papers (see, e.g., Sosnin E A, Avdeev S M, Kuznetzova E A,Lavrent'eva L V. A bacterial barrier-discharge KrBr Excilamp. Instr.Experiment. Tech. 2005; 48:663-66; Matafonova G G, Batoev V B, AstakhovaS A, Gomez M, Christofi N. Efficiency of KrCl excilamp (222 nm) forinactivation of bacteria in suspension. Lett Appl Microbiol 2008;47(6):508-13; and Wang D, Oppenlander T, El-Din M G, Bolton J R.Comparison of the disinfection effects of vacuum-UV (VUV) and UV lighton Bacillus subtilis spores in aqueous suspensions at 172, 222 and 254nm. Photochem Photobiol 2010; 86(1):176-81) have been published on theirbactericidal properties (as expected they are highly efficient), but theconcept that these lamps will kill bacteria but not human cells is notdescribed.

Thus, there may be a need to address at least some of the deficienciesand/or issues that to date remained with respect to the above-describedconventional systems and methods.

SUMMARY OF EXEMPLARY EMBODIMENTS

Accordingly, exemplary embodiments of the apparatus, methods and systemscan be provided that can address at least some of such deficiencies. Forexample, the exemplary embodiments of the apparatus, methods and systemscan use an ultraviolet radiation to selectively affecting and/or killingbacteria while not harming human cells.

In particular, in certain exemplary embodiments of the presentdisclosure, a UV irradiator, e.g., the excilamp, can be provided whichcan effect and/or kill bacteria, without being harmful to human cells.The exemplary system, method and apparatus takes into consideration thatbacteria are typically physically much smaller than human cells, andthus, an appropriately chosen UV wavelength (e.g., around 207 nm to 220nm) preferably penetrates and kills bacteria, but preferably would notbe able to penetrate into the biologically sensitive nucleus of humancells. Irradiating a wound with this exemplary tailored UV radiation,for example, can therefore provide the advantages of UV bacteriologicalsterilization, while being safe for patient and staff, and preferablynot requiring protective clothing/hoods/eye shields, or the like.According to another exemplary embodiment of the present disclosure, theroom air (as opposed to the wound), or surfaces (e.g., walls, floors,ceiling, countertops, furniture, fixtures, etc.) can be exposed to thisexemplary UV lamp in hospital environments.

According to further exemplary embodiments of the present disclosure, itis possible to provide exemplary UV lamps that can emit at a singlewavelength, in contrast to standard mercury UV lamps which typicallyemit over a wide range of wavelengths. The exemplary lamps can includeUV emitted from an excited molecule complex (e.g., an exciplex, such aseither krypton-bromine or krypton-chlorine), called excilamps, and canbe modified in accordance with certain exemplary embodiments of thepresent disclosure to produce UV having a single wavelength, thus,facilitating modifying the UV irradiation to have enough energy topenetrate and kill bacteria, but not enough range to penetrate to thenucleus of human cells. This can be performed based on certain exemplaryembodiments, e.g., using one or more modulators, wavelength-effectingmasks, etc.

Certain exemplary embodiments of the present disclosure can be tested,for example, in an in-vitro (laboratory) human skin system (see, e.g.,Belyakov O V, Mitchell S A, Parikh D, Randers-Pehrson G, Marino S,Amundson S A, et al. Biological effects in unirradiated human tissueinduced by radiation damage up to 1 mm away. Proc. Natl. Acad. Sci.U.S.A. 2005; 102:14203-08; and Su Y, Meador J A, Geard C R, Balajee A S.Analysis of ionizing radiation-induced DNA damage and repair in threedimensional human skin model system. Exp Dermatol 2010; 19(8):e16-22),in an in-vitro wound infection model (see, e.g., Giannini G T, Boothby JT, Sabelman E E. Infected wound model development of an in vitrobiomaterial-protected wound infection model to study microbial activityand antimicrobial treatment through microdialysis. Adv Skin Wound Care2010; 23(8):358-64), in a clinically relevant mouse model of surgicalwound infection (see, e.g., McLoughlin R M, Solinga R M Rich J, ZaleskiK J, Cocchiaro J L, Risley A, et al. CD4+ T cells and CXC chemokinesmodulate the pathogenesis of Staphylococcus aureus wound infections.Proc. Natl. Acad. Sci. U.S.A. 2006; 103(27):10408-13), in a nude mousemodel for in-vivo safety standards, in large animal studies, or instudies in the clinic. The exemplary excilamp wound irradiation canfacilitate a practical and inexpensive approach to significantlyreducing surgical site infections.

According to certain exemplary embodiments of the present disclosure, aUV radiation at approximately 207 nm to 220 nm can be provided, forexample, that can differentially damage and/or killmethicillin-resistant Staphylococcus aureus (MRSA), relative to humancells. Although a conventional germicidal UV lamp can be approximatelyequally efficient at killing MRSA and human cells, by contrast, theexemplary 207 to 220 nm wavelength UV from excilamps can beapproximately 5,000 times more efficient at killing MRSA relative tohuman cells.

According to certain exemplary embodiments of the present disclosure,apparatus and method for generating at least one radiation can beprovided. According to certain exemplary embodiments, the exemplaryapparatus and/or method can selectively kill and/or affect at least onebacteria. For example, a radiation source first arrangement configuredto generate at least one radiation having one or more wavelengthsprovided in a range of about 190 nanometers (nm) to about 230 nm, and atleast one second arrangement configured to substantially prevent the atleast one radiation from having any wavelength that is outside of therange can be provided. The radiation can be configured to selectivelyaffect or destroy at least one bacteria on or within a body, whilesubstantially avoiding harm to cells of the body. The radiation sourcecan include a krypton-bromine lamp or a krypton-chlorine lamp excilamp.Additionally, the radiation source first arrangement can be furtherconfigured to generate the at least one radiation having a singlewavelength provided in the range, and the at least one secondarrangement can be further configured to prevent the radiation fromhaving any wavelength other than the single wavelength. The singlewavelength can be about 207 nm, and/or about 222 nm. Further, the secondarrangement can include at least one of a chemical filter or adielectric.

According to yet another exemplary embodiment, systems and methods canbe provided for generating at least one radiation. For example, e.g.,using a radiation source first arrangement or another arrangement, it ispossible to generate the radiation(s) having one or more wavelengthsprovided in a range of about 190 nanometers (nm) to about 230 nm.Further, it is possible to, using at least one second arrangement and/orthe same arrangement, to substantially prevent the radiation(s) fromhaving any wavelength that is outside of the range.

The radiation(s) can be configured to selectively affect or destroy atleast one bacteria on or within a body, while substantially avoidingharming to any of cells of the body. The radiation source can include anexcilamp, a krypton-bromine lamp and/or a krypton-chlorine lamp. Theradiation source first arrangement can be further configured to generatethe radiation(s) having a single wavelength provided in the range, andthe second arrangement(s) can be further configured to prevent theradiation(s) from having any wavelength other than the singlewavelength. The single wavelength can be about 206 nm, 207 nm, and/or222 nm. The second arrangement can include a chemical filter and/or adielectric.

These and other objects, features and advantages of the presentdisclosure will become apparent upon reading the following detaileddescription of embodiments of the present disclosure in conjunction withthe appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the present disclosure willbecome apparent from the following detailed description taken inconjunction with the accompanying Figures showing illustrativeembodiments of the present disclosure, in which:

FIG. 1 is a graph of an exemplary spectrum of UV wavelengths generatedby a typical mercury UV lamp;

FIG. 2 is an illustration of an exemplary penetration of low wavelengthUV radiation with respect to human cells and bacteria in accordance withan exemplary embodiment of the present disclosure;

FIG. 3 is an illustration of an exemplary excilamp which can provide theUV radiation with at a single wavelength or in a particular range ofwavelengths in accordance with an exemplary embodiment of the presentdisclosure;

FIG. 4 is a graph of the exemplary spectral distributions of the UVradiation generated by excilamps in accordance with certain exemplaryembodiments of the present disclosure;

FIG. 5 is an exemplary block diagram of an apparatus according toparticular exemplary embodiments of the present disclosure;

FIGS. 6(a) and 6(b) are spectral graphs of exemplary excilamps accordingto certain exemplary embodiments of the present disclosure;

FIG. 7 is a graph of human cell survival with respect to ultra violetfluence, according to certain exemplary embodiments of the presentdisclosure;

FIG. 8 is a graph of MRSA survival with respect to an excilamp fluenceaccording to certain exemplary embodiments of the present disclosure;

FIG. 9(a) is a graph of exemplary yields for pre-mutagenic DNS lesionsfor cyclobutane pyrimidine dimers; and

FIG. 9(b) is a graph of exemplary yields for pre-mutagenic DNS lesionsfor pyrimidine-pyrimidone 6-4 photoproducts (6-4PP).

Throughout the drawings, the same reference numerals and characters,unless otherwise stated, are used to denote like features, elements,components, or portions of the illustrated embodiments. Moreover, whilethe present disclosure will now be described in detail with reference tothe figures, it is done so in connection with the illustrativeembodiments and is not limited by the particular embodiments illustratedin the figures and the accompanying claims.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

UV radiations of different wavelengths can have different abilities topenetrate into cells. Typically, the higher the wavelength, the morepenetrating the radiation, and the lower the wavelength, the lesspenetrating the radiation. For example, UV radiation with a lowwavelength of about 200 nm, for example, while able to pass throughwater quite efficiently, can be heavily absorbed in the outer part of ahuman cell (the cytoplasm, see, for example, FIG. 2), and may not haveenough energy to reach the biologically sensitive cell nucleus.

The limited penetrating ability of ˜200 nm UV radiation can be used, asshown in FIG. 2, because bacteria are typically physically far smallerthan human cells. Specifically, a typical bacterial cell is less thanabout 1 μm (micrometer) in diameter, whereas human cells are typicallyabout 10 to 30 μm across, depending on their type and location.

In particular, FIG. 2 shows a typical human cell nucleus having aspherical geometry 202 or a flattened geometry 204, illustrating thepenetration into a human cell of UV radiation with wavelength of around200 nm. As shown in FIG. 2, essentially no UV of this wavelengthpreferably reaches the cell nucleus 202, 204, which contains theradiation-sensitive DNA. Accordingly, UV radiation of this wavelengthwould typically not be harmful to human cells or thus to humans. Inaddition to this geometric reason, there can be a biological reason whyUV with a wavelength around 200 nm UV will typically not be harmful tohumans. At about 185 nm and below, UV can be very efficiently absorbedby oxygen, producing ozone and oxidative damage. Above about 240 nm, UVcan be very efficient at producing oxidative DNA base damage (see, e.g.,Kvam E, Tyrrell R M Induction of oxidative DNA base damage in human skincells by UV and near visible radiation. Carcinogenesis 1997;18(12):2379-84; and Pattison D I, Davies M J. Actions of ultravioletlight on cellular structures. EXS 2006(96):131-57). Thus, 200 nmwavelength UV can be in a narrow UV “safety window”. In contrast,because bacteria are typically physically much smaller in size thanhuman cells, UV radiation with wavelength around 200 nm can penetratethrough, and therefore kill, bacteria.

According to exemplary embodiments of the present disclosure, it ispossible to utilize one or more UV excilamps which, in contrast tostandard UV lamps, can produce UV radiation at a specificwavelength—e.g., around 200 nm. UV radiation around such exemplarywavelength (e.g., a single wavelength or in a range of certainwavelengths as described herein) can penetrate and kill bacteria, butpreferably would not penetrate into the nucleus of human cells, andthus, can be expected to be safe for both patient and staff.

Exemplary Excilamp UV Irradiator

The exemplary excilamp technology can utilize certain exemplary conceptswhich were developed at the Institute of High Current Electronics (IHCE)in Tomsk, Siberia (see, e.g., Sosnin E A, Oppenlander T, Tarasenko V F.Applications of capacitive and barrier discharge excilamps inphotoscience. J. Photochem. Photobiol C: Photochem. Rev. 2006;7:145-63.). Additional exemplary excilamps that can be utilized with theexemplary embodiments of the present disclosure may be available fromHeraeus Noblelight in Germany. The IHCE lamps, an exemplary embodimentof such lamp 302 is shown in FIG. 3, can be small, rugged, cost ˜$1,000,and can be made to produce a variety of single wavelength UV radiations.Based on the considerations above, exemplary embodiments of the presentdisclosure can use, for example, a krypton-bromine lamp excilamp, whichcan produce UV at about 207 nm, or a krypton-chlorine lamp (FIG. 3),which can produce UV at about 222 nm. Another exemplary excilamp canproduce UV at about 206 nm. The exemplary spectrum of these lamps areshown in the graph of FIG. 4. As shown in FIG. 4, a spectraldistribution 402 can be produced by a krypton-bromine lamp, and spectraldistribution 404 was produced by a krypton-chlorine lamp. Additionally,according to further exemplary embodiments of the present disclosure,certain exemplary features can be a filter 304 (e.g., spectrum filteringelements such as multilayer dielectric filters or chemical filters) toremove unwanted wavelengths, or those wavelengths that are outside ofthe preferable range of wavelengths. For example, absorption and/orreflective elements can be provided between the lamp and the irradiatedsurface to filter unwanted wavelengths, such as, e.g., a band-passfilter, a long-wavelength blocking filter. In one exemplary embodiment,the absorptive material can be fluorescent, such that it emits visiblelight when it absorbs UV radiation to provide an indication that thelamp is operating. Alternatively or in addition, other gases can beadded to the lamp to suppress unwanted wavelengths. For example, addingargon to the krypton-chlorine lamp can suppress generation of the 228 nmUV.

The typical power output of the air-cooled excilamps can be about 7.5 to20 mW/cm², although higher power can be obtained in a water-cooledsystem. At about 20 mW/cm², only a few seconds of exposure can deliverabout 20 mJ/cm², which can be a typical bactericidal dose.

Exemplary embodiments of the present disclosure can provide an excilamp,emitting about a 207 nm or about a 222 nm single wavelength UVradiation, to differentially kill bacteria while sparing adjacent humancells. Further, the wavelength(s) of the UV radiation according tofurther exemplary embodiments of the present disclosure can be in therange of about 190 nanometers (nm) to about 230 nm. Exemplaryexperiments implementing embodiments of the present disclosure caninclude: an in-vitro (laboratory) 3-D human skin system (see, e.g.,Belyakov O V, Mitchell S A, Parikh D, Randers-Pehrson G, Marino S,Amundson S A, et al. Biological effects in unirradiated human tissueinduced by radiation damage up to 1 mm away. Proc. Natl. Acad. Sci.U.S.A. 2005; 102:14203-08; and Su Y, Meador J A, Geard C R, Balajee A S.Analysis of ionizing radiation-induced DNA damage and repair inthreedimensional human skin model system. Exp Dermatol 2010;19(8):e16-22); a nude mouse model for in-vivo safety standards; anin-vitro wound infection model (see, e.g., Giannini G T, Boothby J T,Sabelman E E. Infected wound model development of an in vitrobiomaterial-protected wound infection model to study microbial activityand antimicrobial treatment through microdialysis. Adv Skin Wound Care2010; 23(8):358-64); a clinically relevant mouse model of surgical woundinfection (see, e.g., McLoughlin R M Solinga R M Rich J, Zaleski K J,Cocchiaro J L, Risley A, et al. CD4+ T cells and CXC chemokines modulatethe pathogenesis of Staphylococcus aureus wound infections. Proc. Natl.Acad. Sci. U.S.A. 2006; 103(27):10408-13); larger animal model studies;studies in a clinic. According to yet another exemplary embodiment ofthe present disclosure, excilamp irradiation can be provided for awound, a room air and/or surfaces (e.g., walls, floors, ceiling,countertops, furniture, fixtures, etc.), which can facilitate apractical and inexpensive approach to significantly reducing surgicalwound infection.

In an exemplary experiment implementing certain exemplary embodiments ofthe present disclosure, an exemplary test bench was developed forgathering, e.g., exemplary preliminary sterilization results fromexemplary UV light sources. For example, the exemplary test bench caninclude: a) a light-tight box; b) a shutter control; c) a filter holder;and d) adjustable exposure parameters for time, distance, and wavelength(e.g., 207 nm KrBr excilamp, 222 nm, KrCl excilamp, and 254 nm standardgermicidal lamp). Additionally, exemplary custom filters can be designedto eliminate higher-wavelength components in the excilamp emissionspectra to provide optimal single-wavelength exposure. A UV spectrometerand deuterium lamp (e.g., for equipment calibration) can be used tovalidate the filter effectiveness, as shown, for example, in FIGS. 6(a)and 6(b), which illustrate the normalized spectra comparing excilampemission (red—602 a and 602 b) with filtered excilamp emission (blue—604a and 604 b) for both KrBr and KrCl excilamps. This exemplary test benchfacilitated, for example, a generation of biological findings offiltered excilamp exposure to both bacteria and healthy human cells,which are described below. In turn, the exemplary biological testingexperience has provided details regarding exemplary parameters fordeveloping filtered KrBr and KrCl excilamps into optimal devices forclinical applications.

Exemplary Biological Results

Described below are certain exemplary experiments implementing certainexemplary embodiments of the present disclosure. The exemplaryexperiments investigated, for example, whether UV from exemplaryfiltered excilamps can be effective at killing bacteria while sparingnormal human cells.

In the exemplary experiment, human fibroblasts were, for example,exposed to about 3 mJ/cm² from a standard germicidal UV lamp (e.g., 254nm), and their survival was less than about 10⁻⁴. By contrast, when theywere exposed to fluences as high as 150 mJ/cm² from the exemplaryfiltered KrBr or KrCl excilamp (e.g., 207 and 222 nm, respectively),their survival was in the range from about 1 to about 10⁻¹ (see FIG. 7).Indeed, FIG. 7 shows an exemplary graph indicating a clonogenic survivalof normal human skin fibroblasts (AG1522) exposed to UV from exemplaryfiltered KrBr (207 nm) or KrCl (222 nm) excilamps, or from aconventional germicidal lamp (254 nm).

In the exemplary experiment, bactericidal killing efficacy of theexemplary excilamps was tested, for example, on methicillin resistantStaphylococcus aureus (MRSA). MRSA can be the cause of about 25% ofsurgical site infection and can be associated with approximately 20,000deaths per year in the United States, mostly healthcare related. MRSAand antibiotic-susceptible S. aureus are typically equally susceptibleto UV from conventional germicidal lamps. (See, e.g., Conner-Kerr T A,Sullivan P K, Gaillard J, Franklin M E, Jones R M. The effects ofultraviolet radiation on antibiotic-resistant bacteria in vitro. OstomyWound Manage. 1998; 44(10):50-6). The exemplary results are shown, forexample, in FIG. 8, indicating that at an excilamp fluence of about 100mJ/cm², an MRSA survival level of 10⁻⁴ can be achieved. For example,FIG. 8 shows an exemplary graph of MRSA (strain US300) inactivationafter exposure to UV from the exemplary filtered KrBr or KrCl excilamps(207 nm and 222 nm, respectively).

Comparing the exemplary results in FIGS. 7 and 8, the exemplary filteredexcilamp UV radiation at 207 nm and at 222 nm can differentially effectand/or kill MRSA relative to the human cells. For example, at exemplaryfiltered excilamp fluences of about 100 mJ/cm², the survival level ofhuman cells is, for example, in the range of about 0.1 to 1, while thesurvival level of MRSA is in the range of about 10⁻⁴. Such exemplaryfinding are in considerable contrast to the situation for conventiongermicidal UV lamps (GUVL), which is roughly equally efficient atkilling bacteria and human cells. For example, for a conventionalgermicidal UV lamp, at a UV fluence for which a GUVL produces abacterial survival of 10⁻⁴, the human cell survival from the GUVL isabout 0.3×10⁻⁴, a human cell survival advantage of 0.3. With theexemplary excilamp at 207 or 222 nm, at a UV fluence for which theexemplary 207 or 222 nm filtered excilamp produces a bacterial survivalof 10⁻⁴, the human cell survival by the exemplary filtered exilamps isin the range of about 0.1 to 1, a human cell survival advantage in therange of 5,000.

Exemplary Induction of Pre-Mutagenic DNA Lesions in Human Skin

FIGS. 9(a) and 9(b) illustrate the exemplary measured induced yields ofcyclobutane pyrimidine dimers (CPD) lesions (FIG. 9(a)) and 6-4photoproducts (6-4PP, FIG. 9(b)) after exposure of the exemplary 3-Dskin tissue model to the broad UV spectrum from a conventionalgermicidal UV lamp (e.g., peak 254 nm) or to an exemplary 207-nm light905 from the Kr—Br excimer lamp. The exemplary germicidal lamp producedhigh yields of both pre-mutagenic skin DNA lesions. However after 207-nmexposure, neither lesion showed an induced yield which was significantlyelevated above zero, at any of the studied fluences.

The exemplary 207-nm light can kill MRSA much more efficiently than itcan kill human cells. For example at a fluence of approximately 207-nm,the light can produce four logs of MRSA cell kill, and there is muchless than one decade of cell kill in human cells. In contrast with theresults for 207-nm light, while conventional germicidal lamps 910 canefficiently kill MRSA, conventional germicidal lamps are also almost asefficient at killing human cells. Quantitatively, for a four-log levelof MRSA killing, 207-nm UV light can produce about 1,000-fold less humancell killing than a conventional germicidal UVC lamp.

In terms of the safety of 207-nm UV light, the lack of induction oftypical UV-associated pre-mutagenic DNA lesions in the epidermis of a3-D skin model is consistent with biophysical expectations based on thelimited penetration of 207-nm UV light, and consistent with earlierstudies using 193-nm laser light. (See, e.g., Green H, Boll J, Parrish JA, Kochevar I E, Oseroff A R (1987) Cytotoxicity and mutagenicity of lowintensity, 248 and 193 nm excimer laser radiation in mammalian cells.Cancer Res 47: 410-413). While other UV wavelengths have been suggestedas potentially being safe for human exposure, in particular 405 nm (see,e.g., McDonald R S, Gupta S, Maclean M, Ramakrishnan P, Anderson J G, etal. (2013) 405 nm Light exposure of osteoblasts and inactivation ofbacterial isolates from arthroplasty patients: potential for newdisinfection applications? Eur Cell Mater 25: 204-214) and 254 nm (see,e.g., Dai T, Vrahas M S, Murray C K, Hamblin M R (2012) Ultraviolet Cirradiation: an alternative antimicrobial approach to localizedinfections? Expert Rev Anti Infect Ther 10: 185-195), no mechanisms havebeen proposed for a differential toxic effect for bacteria vs. humancells at these wavelengths, and both 405-nm light (see, e.g.,Papadopoulo D, Guillouf C, Mohrenweiser H, Moustacchi E (1990)Hypomutability in Fanconi anemia cells is associated with increaseddeletion frequency at the HPRT locus. Proc Natl Acad Sci USA 87:8383-8387) and 254-nm light (see, e.g., Zolzer F, Kiefer J (1984)Wavelength dependence of inactivation and mutation induction to6-thioguanine-resistance in V79 Chinese hamster fibroblasts. PhotochemPhotobiol 40: 49-53) have been shown to be mutagenic to mammalian cellsat relevant fluences.

In contrast, the exemplary 207-nm light from a Kr-Br excimer lamp canhave considerable potential for safely reducing SSI rates. Such lampscan be used in an operating room environment without the need forprotective clothing for the staff or the patient. For example, 207-nmlight can be used for continuous low-fluence-rate exposure during asurgical procedure, because current evidence suggests that the majorityof SSI can result from bacteria alighting directly onto the surgicalwound from the air. Evidence for the dominance of an airborne route cancome from correlations between the density of airborne bacteria andpostoperative sepsis rates. (See, e.g., Lidwell O M, Lowbury E J, WhyteW, Blowers R, Stanley S J, et al. (1983) Airborne contamination ofwounds in joint replacement operations: the relationship to sepsisrates. J Hosp Infect 4: 111-131; Gosden P E, MacGowan A P, Bannister G C(1998) Importance of air quality and related factors in the preventionof infection in orthopaedic implant surgery. J Hosp Infect 39: 173-180).Evidence for the significance of airborne bacteria alighting directly onthe surgical wound can come from, for example, studies of conventionalUV lamps specifically directed over the surgical site (see, e.g., RitterM A, Olberding E M, Malinzak R A (2007) Ultraviolet lighting duringorthopaedic surgery and the rate of infection. J Bone Joint Surg Am 89:1935-1940), and also wound-directed filtered airflow studies. (See,e.g., Stocks G W, O'Connor D P, Self S D, Marcek G A, Thompson B L(2011) Directed air flow to reduce airborne particulate and bacterialcontamination in the surgical field during total hip arthroplasty. JArthroplasty 26: 771-776).

Thus, a continuous low-fluence-rate exposure of 207-nm UV light onto thesurgical wound area during the complete surgical procedure can killbacteria as they alight onto the wound area. Such exemplary continuousexposure can be designed to inactivate bacteria before the bacteria canpenetrate into the interior of the wound. A second advantage associatedwith targeting bacteria as the bacteria alight onto the wound area is inrelation to biofilms. (See, e.g., Frei E, Hodgkiss-Harlow K, Rossi P J,Edmiston C E, Jr., Bandyk D F (2011) Microbial pathogenesis of bacterialbiofilms: a causative factor of vascular surgical site infection. VascEndovascular Surg 45: 688-696). For example, as bacteria can alight ontothe skin/wound, they can typically be in individual planktonic form, andthus, can be amenable to killing by 207-nm light. This can prevent thesubsequent formation of bacterial clusters (e.g., biofilms), which canbe refractory to 207-nm light as they are to most other therapies.

Several configurations for the exemplary 207-nm lamp in a surgicalsetting can be possible. It is important that surgical staff do notinadvertently block the UV light, so one exemplary arrangement can befor the excimer lamp to be incorporated into a standard overheadsurgical illumination system. A possible second exemplary UV lightsource, to ensure a level of redundancy from inadvertent shielding, canbe incorporation into a surgeon's headlight illumination system, withthe UV light transmitted to the headlight via fiber optics. (See, e.g.,Miller J, Yu X-B, Yu P K, Cringle S J, Yu D-Y (2011) Development of afiber-optic delivery system capable of delivering 213 and 266 nm pulsedNd:YAG laser radiation for tissue ablation in a fluid environment. ApplOpt 50: 876-885).

Commercial 207-nm excimer lamps can be inexpensive and long lived. Infact in a different wavelength range (e.g., 172 nm) xenon excimer lamps(see, e.g., Salvermoser M, Murnick D E (2003) High-efficiency,high-power, stable 172 nm xenon excimer light source. Appl Phys Lett 83:1932-1934) with rated lifetimes of 50,000 to 100,000 hours, are alreadyin commercial use (see, e.g., Hitzschke L, Vollkommer F (2001) Productfamilies based on dielectric barrier discharges. In: Bergman R S,editor. Proceedings of the Ninth International Symposium on the Science& Technology of Light Sources (LS:9). Ithaca, N.Y.: Cornell UniversityPress. pp. 411-421), providing (e.g., using appropriate phosphors) bothinterior and exterior office lighting, for example on the Rotterdam KPNTelecom tower. (See, e.g., Tscherteu G, Lervig M C, Brynskov M KPNTower, Rotterdam, 2000; 2012; Aarhus, Denmark. Media ArchitectureInstitute Vienna/Sydney and Aarhus University).

In addition to direct bactericidal applications in surgicalenvironments, the exemplary 207-nm UV light can be used to treat, on acontinuous basis, any airborne environment where there is a highlikelihood of airborne-based pathogen transmission (e.g., Tuberculosisor the pandemic influenza). While upper-room UV irradiation systems havelong been considered, based on conventional broad-spectrum UV lamps(see, e.g., Reed N G (2010) The history of ultraviolet germicidalirradiation for air disinfection. Public Health Rep 125: 15-27), andhave shown some promise(see, e.g., Nardell E A, Bucher S J, Brickner PW, Wang C, Vincent R L, et al. (2008) Safety of upper-room ultravioletgermicidal air disinfection for room occupants: results from theTuberculosis Ultraviolet Shelter Study. Public Health Rep 123: 52-60;Escombe A R, Moore D A, Gilman R H, Navincopa M, Ticona E, et al. (2009)Upper-room ultraviolet light and negative air ionization to preventtuberculosis transmission. PLoS Med 6: e43), they have not, however,been widely used, in part, because of safety concerns relating topotential low-level broad-spectrum UV exposure. (See, e.g., Nardell E A,Bucher S J, Brickner P W, Wang C, Vincent R L, et al. (2008) Safety ofupper-room ultraviolet germicidal air disinfection for room occupants:results from the Tuberculosis Ultraviolet Shelter Study. Public HealthRep 123: 52-60; Wengraitis S, Reed N G (2012) Ultraviolet spectralreflectance of ceiling tiles, and implication for the safe use ofupper-room ultraviolet germicidal irradiation. Photochem Photobiol 88:1480-1488; Sliney D (2013) Balancing the risk of eye irritation fromUV-C with infection from bioaerosols. Photochem Photobiol 89: 770-776).

FIG. 5 shows an exemplary block diagram of an exemplary embodiment of asystem according to the present disclosure. For example, exemplaryprocedures in accordance with the present disclosure described hereincan be performed by or controlled using a UV generation source 580and/or hardware processing arrangement and/or a computing arrangement510, separately and in conjunction with one another. Such exemplaryprocessing/computing arrangement 510 can be, e.g., entirely or a partof, or include, but not limited to, a computer/processor 520 that caninclude, e.g., one or more microprocessors, and use instructions storedon a computer-accessible medium (e.g., RAM, ROM, hard drive, or otherstorage device).

As shown in FIG. 5, e.g., a computer-accessible medium 530 (e.g., asdescribed herein above, a storage device such as a hard disk, floppydisk, memory stick, CD-ROM, RAM, ROM, etc., or a collection thereof) canbe provided (e.g., in communication with the processing arrangement510). The computer-accessible medium 530 can contain executableinstructions 540 thereon. In addition or alternatively, a storagearrangement 550 can be provided separately from the computer-accessiblemedium 530, which can provide the instructions to the processingarrangement 510 so as to configure the processing arrangement to executecertain exemplary procedures, processes and methods, as described hereinabove, for example.

Further, the exemplary processing arrangement 510 can be provided withor include an input/output arrangement 570, which can include, e.g., awired network, a wireless network, the internet, an intranet, a datacollection probe, a sensor, etc. As shown in FIG. 5, the exemplaryprocessing arrangement 510 can be in communication with an exemplarydisplay arrangement 560, which, according to certain exemplaryembodiments of the present disclosure, can be a touch-screen configuredfor inputting information to the processing arrangement in addition tooutputting information from the processing arrangement, for example.Further, the exemplary display 560 and/or a storage arrangement 550 canbe used to display and/or store data in a user-accessible format and/oruser-readable format.

The foregoing merely illustrates the principles of the disclosure.Various modifications and alterations to the described embodiments willbe apparent to those skilled in the art in view of the teachings herein.It will thus be appreciated that those skilled in the art will be ableto devise numerous systems, arrangements, and procedures which, althoughnot explicitly shown or described herein, embody the principles of thedisclosure and can be thus within the spirit and scope of thedisclosure. In addition, all publications and references referred toabove can be incorporated herein by reference in their entireties. Itshould be understood that the exemplary procedures described herein canbe stored on any computer accessible medium, including a hard drive,RAM, ROM, removable disks, CD-ROM, memory sticks, etc., and executed bya processing arrangement and/or computing arrangement which can beand/or include a hardware processors, microprocessor, mini, macro,mainframe, etc., including a plurality and/or combination thereof. Inaddition, certain terms used in the present disclosure, including thespecification, drawings and claims thereof, can be used synonymously incertain instances, including, but not limited to, e.g., data andinformation. It should be understood that, while these words, and/orother words that can be synonymous to one another, can be usedsynonymously herein, that there can be instances when such words can beintended to not be used synonymously. Further, to the extent that theprior art knowledge has not been explicitly incorporated by referenceherein above, it can be explicitly being incorporated herein in itsentirety. All publications referenced can be incorporated herein byreference in their entireties.

What is claimed is:
 1. A method for selectively killing or destroying atleast one bacteria at a medical treatment site or in a medical treatmentenvironment, comprising: generating, with at least one excilamp, atleast one bactericidal radiation configured to selectively kill ordestroy the at least one bacteria on or within a body, while avoidingharm to cells of the body, wherein the at least one bactericidalradiation has at least one wavelength that is in a range of 190nanometers (nm) to 230 nm, and wherein a peak wavelength of the at leastone bactericidal radiation is at least one of approximately at 207 nm orapproximately at 222 nm; filtering, with a filter arrangement comprisingat least one of a band pass filter or a combination of a low pass filterand a high pass filter, the at least one bactericidal radiation toprevent all ultraviolet wavelengths that are outside of the range frompassing through the filter arrangement; allowing all wavelengths in therange of 190 nm to 230 nm to be provided to the body; fluorescingvisible light to indicate that the at least one excilamp is operating;and irradiating the at least one bacteria using the allowed wavelengthsand selectively killing or destroying the at least one bacteria.
 2. Themethod of claim 1, further comprising directing the at least onebactericidal radiation using the at least one excilamp.
 3. The method ofclaim 1, wherein the at least one excilamp includes at least one of akrypton-bromine lamp or a krypton-chlorine lamp.
 4. The method of claim1, wherein the filter arrangement includes at least one of a chemicalfilter or a dielectric filter.
 5. The method of claim 1, wherein thefiltering the at least one bactericidal radiation to prevent allultraviolet wavelengths that are outside of the range from passingthrough the filter arrangement includes filtering out the at least onebactericidal radiation that has a peak wavelength outside of the range.6. The method of claim 1, wherein the selectively killing or destroyingthe at least one bacteria includes, at a same time, avoiding harm tocells of the body.
 7. The method of claim 6, wherein the allowing allwavelengths in the range of 190 nm to 230 nm comprises allowing everyallowed wavelength to pass therethrough.
 8. The method of claim 1,further comprising providing the at least one bactericidal radiationfrom within a housing through a window thereof in a first direction thatis approximately parallel to a second direction of irradiation of the atleast one radiation through the window.
 9. The method of claim 1,further comprising providing the at least one bactericidal radiationfrom within a housing through a window thereof in a first direction thatis approximately parallel to a second direction of irradiation of the atleast one radiation through the window.
 10. The method of claim 1,wherein the allowing all wavelengths in the range of 190 nm to 230 nmcomprises allowing every allowed wavelength to pass therethrough. 11.The method according to claim 1, wherein at least one of bacteria has acell diameter that is less than 1 μm, and wherein the generation or thefiltering comprises modifying the at least one bactericidal radiation topenetrate and kill the at least one, and preventing a penetration of anucleus of human cells that are approximately at a diameter of 10 μm and30 μm.